Reactions

The first step in the bulk product or Active Pharmaceutical Ingredient (API) process is the reaction stage, which can be broken up into chemical synthesis or biotechnology depending on the type of drug being produced.

Chemical Synthesis

Batch Reactor

Batch reactors
can range in size from 500 liters to 16 cubic meters depending on the scale of production for the API. Since contamination is a major concern in the pharmaceutical industry these reactors are normally made from stainless steel or glass lined mild steel and are fitted with a manway for easy cleaning. Reactions can be carried out in temperature s ranging from -25°C and 160°C and the pressure can vary from a full vacuum to 6 bar. These reactions are very sensitive to the environment, especially temperature changes, which can cause the product to be contaminated. To prevent contamination external jackets or pipe coils are fitted on the reactor for temperature adjustments. The coil or jacket usually contains a fluid that transfers the heat to the reactor. Agitation is also used in the reactor to provide mixing and heat transfer.

(Copyright Pfaudler Inc., Rochester, NY)

Loop Reactor

A loop reactor is a variation of a
continuously stirred tank reactor
, which is used for gas-liquid reactions at high pressures. Of the three types of loop reactors, jet, gas lift, and propeller, the jet loop reactor is the most common in chemical synthesis. This is because this type of loop reactor has higher heat and mass transfer rates and is easier to scale up. The jet loop reactor operates by injecting a heated, pressurized, liquid with a catalyst through the top or bottom of the reactor. The liquid is then fed through a loop inside the reactor where it interacts with the reactants to begin the reaction. The products that form gather at the bottom of the loop, where they are released from the system. As the liquid evaporates the catalyst is recycled to a small tank where it is diluted and fed back into the reactor.

Batch Autoclave

The batch autoclave is a special type of
batch reactor
that is used for high pressure reactions or for feeds that are solids or slurry. These reactors can run reactions above 5,000 psi and 500°C. These reactors are normally equipped with a magnetically driven stirring system to ensure even heat exchange. They also have computer operated sensors and valves so that the whole system can be monitored from behind a blast wall, given the extremely high pressures. When heating is needed they can be equipped with a heating element.

Biotechnology

Fermenter

are used in API manufacturing to produce antibiotics by microbial fermentation. The process is characterized by fast growth rates, which can lead to mass and heat transfer issues. To account for this often a stirred tank or sparged tank fermenter is used. A stirred tank uses a mechanical agitator to mix the components of the reaction to aid the mass and heat process. A sparged tank does not use a mechanical agitator but use a gas stream to circulate the reactants in the fermenter. Both of these reactors undergo aerobic fermentation and therefore can only be used in aerobic API processes. For anaerobic processes an open tank design is used since the microorganisms produce a foam covering of carbon dioxide which blocks the oxygen from the reactants.